Intravenous ketamine has become a widely used option for individuals with treatment resistant depression who have not improved with traditional antidepressants. While clinical trials demonstrate rapid symptom relief for many patients, less is known about how ketamine performs in everyday clinical settings, where people often present with complex symptoms, comorbid anxiety, and other psychiatric conditions. A new real world study helps clarify how depression and anxiety symptoms evolve over time during ketamine treatment and why patient responses can vary so widely.
What This Real World Study Looked At
Researchers reviewed clinical records from 209 adults with treatment resistant depression who received intravenous ketamine at a specialized interventional psychiatry program. Patients underwent either four or six ketamine infusions administered over a two to three week period.
Depression symptoms were measured using the Montgomery Åsberg Depression Rating Scale, while anxiety symptoms were assessed using the GAD 7 scale. Rather than focusing only on average symptom improvement, the research team applied advanced statistical modeling to identify distinct patterns of symptom change over time, often referred to as symptom trajectories.
Depression and Anxiety Improve but Not at the Same Pace
Overall, patients experienced statistically significant reductions in both depression and anxiety symptoms during ketamine treatment. However, the degree and timing of improvement varied substantially between individuals. Four distinct symptom trajectories were identified for both depression and anxiety.
Some patients showed rapid and robust improvement, while others demonstrated slower or more modest symptom reductions. Anxiety symptoms generally improved more gradually and less consistently than depressive symptoms. This finding suggests that ketamine may influence mood and anxiety through overlapping but partially distinct neurobiological mechanisms.
Does More Ketamine Mean Better Results
Patients who received six infusions showed higher response and remission rates compared to those who received four infusions. Response was defined as a reduction of at least fifty percent in symptom severity, while remission reflected very low symptom scores. However, these differences did not reach statistical significance, meaning the study could not conclusively determine that six infusions were superior.
Importantly, follow up assessments at one week and one month were only available for patients in the four infusion group. This limitation prevented direct comparison of long term durability between the two dosing schedules.
Why Individualized Care Matters
One of the most important findings was the substantial heterogeneity in treatment response. Patients did not follow a uniform trajectory, even when receiving the same ketamine protocol. This supports the growing emphasis on measurement based care, in which clinicians monitor symptoms at each visit and adjust treatment strategies in response to individual progress.
For some patients, additional infusions or alternative approaches may be appropriate. Others may achieve meaningful benefit early in the treatment course. This variability underscores the importance of flexibility and ongoing assessment in ketamine therapy.
What This Means for Clinics and Patients
For clinicians, these findings reinforce the need to set realistic expectations and to track both depression and anxiety symptoms throughout treatment. Ketamine can produce meaningful clinical improvements, but responses are often modest and vary widely between individuals.
For patients, the results highlight that lack of immediate response does not necessarily indicate treatment failure. Anxiety symptoms, in particular, may take longer to improve than mood symptoms. Real world evidence such as this helps bridge the gap between controlled clinical trials and routine psychiatric practice.
Looking Ahead in Ketamine Research
Future studies will need to clarify how long ketamine benefits persist following different infusion schedules and how clinicians can better predict individual response. As ketamine clinics continue to expand, real world data will play an essential role in refining protocols and improving outcomes.
Personalized, data driven approaches appear critical for maximizing the therapeutic potential of ketamine in treatment resistant depression.
Read more at https://interventionalpsychiatry.org/
Citations
Janssen Aguilar R, Joseph J, Al Shamali H, et al. Symptom trajectories and clinical outcomes of intravenous ketamine in treatment resistant depression. Journal of Affective Disorders. 2026.
https://doi.org/10.1016/j.jad.2026.121230
McIntyre RS, Rosenblat JD, Nemeroff CB, et al. Synthesizing the evidence for ketamine and esketamine in treatment resistant depression. American Journal of Psychiatry. 2021.
https://doi.org/10.1176/appi.ajp.2020.20081251